CN1314417C - Chinese medicine preparation for treating apoplexia and chest Bi-syndrome and its preparing method - Google Patents
Chinese medicine preparation for treating apoplexia and chest Bi-syndrome and its preparing method Download PDFInfo
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- CN1314417C CN1314417C CNB2004100408055A CN200410040805A CN1314417C CN 1314417 C CN1314417 C CN 1314417C CN B2004100408055 A CNB2004100408055 A CN B2004100408055A CN 200410040805 A CN200410040805 A CN 200410040805A CN 1314417 C CN1314417 C CN 1314417C
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- Medicinal Preparation (AREA)
Abstract
The present invention discloses a Chinese medical preparation and a preparation method thereof, and the Chinese medical preparation is used for treating apoplexy and chest impediment and is prepared from sixteen kinds of Chinese herbal materials of milkvetch root, red sage root, angelica, hemlock parsley, red peony root, etc. The present invention has the effect of supplementing qi, activating blood circulation, dispersing blood stasis and dredging collaterals, mainly treats collateral apoplexy, hemiplegia, limb numbness, the deviated eyes and mouth, stiff tongue and sluggish speech, chest impediment, heart pain, oppression in chest, palpitation and breath shortness caused by qi vacuity blood stagnation and collateral obstruction, and also treats cerebral infarction and coronary heart disease angina pectoris. Compared with the prior art, the present invention has the characteristics of small dose, refining technology, high effect realization time and conspicuous curative effect.
Description
Technical field: the present invention relates to a kind of Chinese medicine preparation and preparation method thereof, particularly a kind of Chinese medicine preparation that is used for the treatment of the apoplexy and the thoracic obstruction and preparation method thereof belongs to technical field of Chinese medicine.
Background technology: the apoplexy and the thoracic obstruction are cardiovascular and cerebrovascular disease, are the particularly commonly encountered diseases and the frequently-occurring diseases of middle-aged and elderly people health of serious harm human health, still do not have good radical-ability medicine at present.The applicant has submitted to a name to be called the patent application of " a kind of Chinese medicinal capsule agent and method for making thereof that can be used for treating apoplexy and breast fraud " August 20 calendar year 2001 to Patent Office of the People's Republic of China, and open on April 2nd, 2003, and publication number is 1406609.It is to be used as medicine with crude drug by 16 flavor Chinese herbal medicine such as the Radix Astragali, Radix Salviae Miltiorrhizae, Radix Angelicae Sinensis, Rhizoma Chuanxiong, Radix Paeoniae Rubra to be prepared from capsule.But capsule can not satisfy the demand of doctor and patient fully, and particularly some patients are unwilling to take capsule; In addition the onset time of capsule long, taking dose is big, also is the subject matter that prior art exists; In addition, we find that in practice because the technology that provides in this patent application document is thicker, the product curative effect that obtains is still not ideal enough.Therefore, we through research repeatedly, finish the present invention on original basis.
Summary of the invention: the purpose of this invention is to provide that a kind of dosage is littler, technology is more smart, onset is faster, the Chinese medicine preparation that is used for the treatment of the apoplexy and the thoracic obstruction of better efficacy and preparation method thereof, especially for soft capsule and the dropping pill formulation and their preparation method of the treatment apoplexy and the thoracic obstruction, to solve problems of the prior art.
The present invention constitutes like this: it mainly is to use following bulk drugs: Radix Astragali 40-90 part, Radix Paeoniae Rubra 15-40 part, Radix Salviae Miltiorrhizae 15-40 part, Radix Angelicae Sinensis 15-40 part, Rhizoma Chuanxiong 15-40 part, Semen Persicae 15-40 part, Flos Carthami 8-20 part, Olibanum (processed) 8-20 part, Myrrha (processed) 8-20 part, Caulis Spatholobi 10-30 part, Radix Achyranthis Bidentatae 15-40 part, Ramulus Cinnamomi 10-30 part, Ramulus Mori 15-40 part, Pheretima 15-40 part, Scorpio 8-20 part and Hirudo 15-40 part are prepared into soft capsule or drop pill.Concrete, it mainly is by following bulk drugs: 66 parts of the Radixs Astragali, 27 parts of Radix Paeoniae Rubra, 27 parts of Radix Salviae Miltiorrhizaes, 27 parts of Radix Angelicae Sinensis, 27 parts of Rhizoma Chuanxiongs, 27 parts in Semen Persicae, 13 parts on Flos Carthami, 13 parts of Olibanum (processed)s, 13 parts of Myrrha (processed)s, 20 parts of Caulis Spatholobis, 27 parts of Radix Achyranthis Bidentataes, 20 parts of Ramulus Cinnamomi, 27 parts of Ramulus Moris, 27 parts of Pheretimas, 13 parts of Scorpios and Hirudo are prepared into soft capsule or drop pill for 27 parts.The preparation method of the Chinese medicine preparation of this treatment apoplexy and the thoracic obstruction is: adopt the supercritical fluid extraction Rhizoma Chuanxiong, Radix Angelicae Sinensis, Ramulus Cinnamomi, Olibanum, the fat-soluble effective ingredient of tanshinone in volatile oil component in the Myrrha and the Radix Salviae Miltiorrhizae, Pheretima, Scorpio, Hirudo takes percolation to carry peptide class isoreactivity material, then with Radix Paeoniae Rubra, the Radix Astragali, Flos Carthami, Semen Persicae, Ramulus Mori, Radix Achyranthis Bidentatae, medicinal residues water boiling and extraction aqueous soluble active constituent behind medicinal residues and the percolation behind Caulis Spatholobi medicinal material coarse powder and the supercritical extraction, the reuse alcohol deposition method removes destarching, phlegmatic temperament, water-solubility impurities such as natural gum class add different adjuvants at last respectively and make soft capsule or drop pill.
Soft capsule of the present invention can prepare like this: get Rhizoma Chuanxiong, Radix Angelicae Sinensis, Ramulus Cinnamomi, Olibanum, Myrrha coarse powder supercritical extraction, get Radix Salviae Miltiorrhizae coarse powder supercritical extraction, it is standby to merge two stage extracts; Scorpio, Hirudo, Pheretima add ethanol percolation, and it is standby to collect percolate; Get Radix Paeoniae Rubra, the Radix Astragali, Flos Carthami, Semen Persicae, Ramulus Mori, Radix Achyranthis Bidentatae, Caulis Spatholobi, with the medical material merging behind supercritical extraction and the percolation, water decocts, filtrate decompression concentrates the back precipitate with ethanol, supernatant and percolate are merged concentrating under reduced pressure, spray drying, get dry powder, add supercritical extract, PEG400, colloid mill grinds, glue, the encapsulating machine pelleting, promptly.Particularly, get Rhizoma Chuanxiong, Radix Angelicae Sinensis, Ramulus Cinnamomi, Olibanum, Myrrha coarse powder supercritical extraction, extracting pressure 28Mpa, 40 ℃ of extraction temperature extracted 2 hours, and extract is standby; Get Radix Salviae Miltiorrhizae coarse powder supercritical extraction, extracting pressure 30Mpa, 40 ℃ of extraction temperature are used dehydrated alcohol/medical material, and the dehydrated alcohol of ml/g 30% amount extracted 2 hours as entrainer, and extract is standby behind the recovery solvent.It is standby to merge two stage extracts.Get Scorpio, Hirudo, Pheretima medical material, powder becomes coarse powder, adds a certain amount of ethanol/medical material, and g/g 70% alcohol dipping was carried out percolation after 24 hours, collects 10 times of percolates, and percolate is standby.Get Radix Paeoniae Rubra, the Radix Astragali, Flos Carthami, Semen Persicae, Ramulus Mori, Radix Achyranthis Bidentatae, Caulis Spatholobi medical material, powder becomes coarse powder, with the medical material merging behind supercritical extraction and the percolation, decoct 2 times, add the water of 12 times of amounts, each 2 hours at every turn, filtered through gauze merges filtrate, and being evaporated to 60 ℃ of relative densities is 1.05, add 95% ethanol to contain alcohol 65% after, left standstill 24 hours, supernatant and percolate are merged, being evaporated to 60 ℃ of relative densities is 1.1, spray drying, it is standby promptly to get dry powder.Got the dry powder and the supercritical extract of 140 mesh sieves, and added PEG-400, after stirring, colloid mill grinds, promptly.In gelatin: glycerol: water is 1: 0.3: 1 ratio glue, adopts the encapsulating machine pelleting, promptly.
Drop pill of the present invention can prepare like this: get Rhizoma Chuanxiong, Radix Angelicae Sinensis, Ramulus Cinnamomi, Olibanum, Myrrha coarse powder supercritical extraction, get Radix Salviae Miltiorrhizae coarse powder supercritical extraction, it is standby to merge two stage extracts: Scorpio, Hirudo, Pheretima add ethanol percolation, and it is standby to collect percolate; Get Radix Paeoniae Rubra, the Radix Astragali, Flos Carthami, Semen Persicae, Ramulus Mori, Radix Achyranthis Bidentatae, Caulis Spatholobi, with the medical material merging behind supercritical extraction and the percolation, water decocts, filtrate decompression concentrates the back precipitate with ethanol, and supernatant and percolate are merged concentrating under reduced pressure, spray drying gets dry powder, after sieving, add in the fused Macrogol 4000, stir, add supercritical extract again, stir the back and add in the drop pill machine, drip and make ball, promptly.Particularly, get Rhizoma Chuanxiong, Radix Angelicae Sinensis, Ramulus Cinnamomi, Olibanum, Myrrha coarse powder supercritical extraction, extracting pressure 28Mpa, 40 ℃ of extraction temperature extracted 2 hours, and extract is standby; Get Radix Salviae Miltiorrhizae coarse powder supercritical extraction, extracting pressure 30Mpa, 40 ℃ of extraction temperature are used dehydrated alcohol/medical material, and the dehydrated alcohol of ml/g 30% amount extracted 2 hours as entrainer, and extract is standby behind the recovery solvent.Get Scorpio, Hirudo, Pheretima coarse powder and add ethanol/medical material, ml/g 70% alcohol dipping was carried out percolation with the speed of 5ml/min/kg after 24 hours, and it is standby to collect 10 times of amount percolates.Get behind Radix Paeoniae Rubra, the Radix Astragali, Flos Carthami, Semen Persicae, Ramulus Mori, Radix Achyranthis Bidentatae, Caulis Spatholobi medicinal material coarse powder and the supercritical extraction that medicinal residues merge behind the medicinal residues and percolation, soak after 3 hours, the water that adds 12 times of amounts, decoct twice, each 2 hours, collecting decoction, being evaporated to 60 ℃ of relative densities is 1.05, and adding 95% ethanol is 65% to containing the alcohol amount, leaves standstill 24 hours, draw the supernatant, subnatant is centrifugal, and centrifugal back supernatant and the supernatant and percolate are merged, and being evaporated to 60 ℃ of relative densities is 1.1, spray drying promptly gets solid content.After crossing 120 mesh sieves, add in 3 times of fused Macrogol 4000s of amount, stir, make to be uniformly dispersed, add supercritical extract again, stir the back and add in the drop pill machine material-storage jar, keep 80 ℃ of fluid temperature, 60 ℃ of water dropper temperature are regulated and are dripped speed, drip and make ball.
Supercritical methanol technology is extracted volatile oil in Radix Angelicae Sinensis, Rhizoma Chuanxiong, Olibanum, Myrrha, the Ramulus Cinnamomi, and this constituents has analgesia, regulates effects such as cardiovascular function, anticoagulation.Water is carried as the pyrazine Alkaloid ligustrazine in the Rhizoma Chuanxiong again, has the adjusting cardiovascular function, improves hemorheological property and microcirculation, anticoagulant and thrombosis; Ferulic acid as in Radix Angelicae Sinensis and the Rhizoma Chuanxiong has antiplatelet aggregative activity.Radix Salviae Miltiorrhizae contains crystallinity furo phenanthrenequione class pigment liposoluble constituent, as tanshinone, select for use supercritical methanol technology to extract, and carry flavones ingredient in the Flos Carthami with phenolic constituents such as water extraction red sage root water soluble ingredient danshensu, protocatechualdehyde and water, the expansible coronary artery of these compositions, blood flow increasing, the formation of microcirculation improvement, antiplatelet aggregation and thrombosis.Use some glycoside active component of water boiling and extraction in addition, as the peoniflorin in the Radix Paeoniae Rubra, the astragaloside in the Radix Astragali, the radix achyranthis bidentatae saponin in the Radix Achyranthis Bidentatae, the cyanogen glycosides of Semen Persicae; These compositions have confirmed physiologically active preferably.Pheretima, Scorpio, Hirudo are selected percolation for use, reuse water extraction polypeptide active component, and this constituents has thrombolytic effect, can improve sanguimotor function.The present invention directly is used as medicine prior art with crude drug and is made into to be used as medicine with extract, by effective component extracting, removes wherein a large amount of non-active ingredients, and curative effect improves greatly, so can reach the purpose that reduces clinical taking dose on the basis that guarantees curative effect.
Adopt the water-soluble polyethylene glycol solid dispersion technology, improved the solubility property of medicine, accelerate dissolution rate, improve bioavailability, improved clinical efficacy, and reached quick-acting purposes.
Be example now, its main pharmacodynamics be described with the soft capsule:
One, the influence that the rat local cerebral ischemia is damaged
1,50 of rats are divided into sham operated rats (PEG400) at random, model control group (PEG400), Capsules group of the present invention (280mg/kg), soft capsule small dose group of the present invention (30mg/kg), middle dosage group (60mg/kg), heavy dose of group (120mg/kg), 10 every group.Continuously gastric infusion is 3 days, and fasting is 16 hours after the administration in the 2nd day, and the last administration is after 90 minutes, and chloral hydrate (360mg/kg, ip) anesthesia separates right carotid, and folder closes in the neck, common carotid artery, external carotid artery proximal part and distal end ligation, cut off the centre.The external carotid artery free-end is pulled to internal carotid artery in alignment, bolt line (selecting diameter 0.24mm nylon wire for use, length 5.0cm) is inserted into intracranial by external carotid artery, stop when meeting slight resistance, insertion depth is about 2cm.Ligation external carotid artery opening, and open the common carotid artery bulldog clamp, the disinfection and stitching wound causes right side middle cerebral artery ischemia model; Sham operated rats is only carried out the separation (above experiment is all carried out at 23 ℃～25 ℃) of right carotid, internal carotid artery, external carotid artery.The behavior disorder of rat is observed and write down to the standard that reaches as follows after 24 hours: (1) is carried the Mus tail and is observed forelimb flexing situation, stretch to ground as two forelimb symmetries, count 0 fen, as the offside forelimb of performing the operation the wrist flexing occurs and counts 1 fen, the elbow flexing is counted 2 fens, and the shoulder inward turning is counted 3 fens, existing wrist flexing and/or elbow flexing, shoulder inward turning person is arranged again, count 4 fens.(2) animal is placed on the plane earth, push away both shoulders respectively, check resistance to side shifting.As bilateral resistance equity and strong, count 0 fen, as resistance descender when the operation offside promotes, according to decline degree difference be divided into gently, in, weigh three degree, count 1,2 and 3 fen respectively.(3) the two forelimbs of animal are put on the wire netting, observed the muscular tension of two forelimbs.Two muscle of anterior limb tension force equities and strong person count 0 fen.Count 1,2 and 3 fen according to operation offside muscular tension decline degree difference equally.(4) animal has ceaselessly to a side person of turn-taking, and counts 1 fen.According to the standard scoring, full marks are 11 minutes, and mark is high more, and expression animal behavior obstacle is serious more.Data are represented with x ± SD, carry out statistical test with the reference differential technique.
Put to death rat behind the behavior scoring, get brain, remove olfactory bulb, cerebellum and low brain stem, crownly be cut into 5, the brain sheet takes on a red color after normal structure is dyed with red tetrazolium (TTC) dyeing, and blocking tissue is white in color, taking a picture in dyeing back, asks the infarct size ratio with Chinese Aero-Space university pathological image analysis software.Data are represented with x ± SD, and are compared the T-test check with the blank group.
The influence that table 1 soft capsule of the present invention damages the rat local cerebral ischemia (x ± SD, n=10)
| Group | Behavior disorder | Ischemic areas (%) |
| Dosage group soft capsule small dose group of the present invention in the heavy dose of group of the sham-operation group model control group Capsules group of the present invention soft capsule of the present invention soft capsule of the present invention | 0 9.7±1.1 7.0±2.3* 6.1±3.0** 7.4±2.2* # 8.5±1.8 | 0 23.9±4.5 18.9±4.2* 15.3±4.6** 18.1±3.3* # 21.1±5.1 |
Compare * P＜0.05, * * P＜0.01 with model control group; Compare with capsule of the present invention
#P＞0.05
The result is as shown in table 1, and ischemia is after 24 hours, and rat model shows tangible behavior disorder, and tangible kitchen range shape ischemic region also appears in rat cerebral tissue, and necrosis area reaches about 25% of full brain; Give the soft capsule of the present invention of various dose, the animal behavior obstacle has alleviating in various degree, and rat cerebral ischemia district necrosis area also has obvious reduction, and is dose dependent; This result shows: the soft capsule of the present invention of same materials medicine and capsule action intensity be (P＞0.05) quite.
2, animal is divided into sham operated rats (medical Oleum Glycines) at random, model control group (medical Oleum Glycines), Capsules group of the present invention (280mg/kg), soft capsule group of the present invention (60mg/kg), 90 every group.Continuously gastric infusion is 3 days, and behind the 1st gastric infusion every 8 hours, respectively give and get 10 rats in batches, chloral hydrate (360mg/kg, ip) anesthesia separates right carotid, folder closes in the neck, common carotid artery, external carotid artery proximal part and distal end ligation, and cut off the centre.The external carotid artery free-end is pulled to internal carotid artery in alignment, bolt line (selecting diameter 0.24mm nylon wire for use, length 5.0cm) is inserted into intracranial by external carotid artery, stop when meeting slight resistance, insertion depth is about 2cm.Ligation external carotid artery opening, and open the common carotid artery bulldog clamp, the disinfection and stitching wound causes right side middle cerebral artery ischemia model; Sham operated rats is only carried out the separation (above experiment is all carried out at 23 ℃～25 ℃) of right carotid, internal carotid artery, external carotid artery.And reached in postoperative that standard is observed and the behavior disorder of record rat in 24 hours as follows: (1) is carried the Mus tail and is observed forelimb flexing situation, stretch to ground as two forelimb symmetries, count 0 fen, as the offside forelimb of performing the operation the wrist flexing occurs and counts 1 fen, the elbow flexing is counted 2 fens, and the shoulder inward turning is counted 3 fens, existing wrist flexing and/or elbow flexing, shoulder inward turning person is arranged again, count 4 fens.(2) animal is placed on the plane earth, push away both shoulders respectively, check resistance to side shifting.As bilateral resistance equity and strong, count 0 fen, as resistance descender when the operation offside promotes, according to decline degree difference be divided into gently, in, weigh three degree, count 1,2 and 3 fen respectively.(3) the two forelimbs of animal are put on the wire netting, observed the muscular tension of two forelimbs.Two muscle of anterior limb tension force equities and strong person count 0 fen.Count 1,2 and 3 fen according to operation offside muscular tension decline degree difference equally.(4) animal has ceaselessly to a side person of turn-taking, and counts 1 fen.According to the standard scoring, full marks are 11 minutes, and mark is high more, and expression animal behavior obstacle is serious more.Data are represented with x ± SD, carry out statistical test with the reference differential technique.
Put to death rat behind the behavior scoring, get brain, remove olfactory bulb, cerebellum and low brain stem, crownly be cut into 5, the brain sheet takes on a red color after normal structure is dyed with red tetrazolium (TTC) dyeing, and blocking tissue is white in color, taking a picture in dyeing back, asks the infarct size ratio with Chinese Aero-Space university pathological image analysis software.And after observing 8h, 16h after the administration, 24h, 32h, 40h, 48h, 56h, 64h, 72h respectively, the weight in wet base of thrombosis, the onset time and the speed of observing capsule of the present invention and soft capsule.
Data are represented with x ± SD, and are compared the T-test check with the blank group.
The influence of table 2 pair rats with cerebral ischemia behavior disorder (x ± SD, n=10)
| Group | 8h | 16h | 24h | 32h | 40h | 48h | 56h | 64h | 72h |
| Sham operated rats | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Model control group | 9.6±1.9 | 9.7±1.3 | 9.6±1.7 | 9.7±1.2 | 9.6±1.5 | 9.7±1.7 | 9.7±1.4 | 9.8±1.1 | 9.7±1.1 |
| Capsules group of the present invention | 9.5±1.8 | 9.4±2.0 | 9.4±1.9 | 9.4±1.8 | 9.0±1.6 | 8.5±1.9 | 8.2±1.4* | 7.5±2.2** | 7.0±2.3** |
| Soft capsule group of the present invention | 9.5±1.7 | 9.4±2.1 | 9.3±1.7 | 9.3±2.2 | 8.5±1.4 | 8.2±1.3* | 8.0±1.7* | 7.4±2.1** | 7.1±2.5** |
The influence of table 3 pair rats with cerebral ischemia ischemic areas (x ± SD, n=10)
| Group | 8h | 16h | 24h | 32h | 40h | 48h | 56h | 64h | 72h |
| Sham operated rats | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Model control group | 22.7±5.1 | 23.5±4.7 | 24.3±4.8 | 23.4±4.5 | 23.4±4.7 | 23.8±5.0 | 24.1±5.1 | 23.1±4.6 | 22.7±5.2 |
| Capsules group of the present invention | 22.1±4.8 | 22.4±4.5 | 23.1±4.9 | 22.1±4.8 | 21.8±4.3 | 20.9±5.4 | 20.1±3.7 | 19.4±5.0* | 18.9±4.2* |
| Soft capsule group of the present invention | 22.5±5.0 | 22.1±3.9 | 22.9±5.1 | 21.7±3.8 | 21.5±4.4 | 20.1±5.0 | 20.1±3.3* | 18.7±4.8* | 18.1±3.3* |
Compare * P＜0.05, * * P＜0.01 with model control group.
The result is shown in table 2 and table 3, and ischemia is after 24 hours, and rat model shows tangible behavior disorder, and tangible kitchen range shape ischemic region also appears in rat cerebral tissue, and necrosis area reaches about 25% of full brain; Give capsule of the present invention and soft capsule of the present invention, the animal behavior obstacle has alleviating in various degree, rat cerebral ischemia district necrosis area also has obvious reduction, but the soft capsule of the present invention of same materials medicine on onset time early than capsule of the present invention (soft capsule of the present invention is the 48h onset after administration, and Capsules group is then in the 56h onset).
Two, to the influence of rat heart muscle ischemic injuries
Get 50 of rats, be divided into blank group (PEG400), capsule of the present invention (280mg/kg), soft capsule small dose group of the present invention (30mg/kg), middle dosage group (60mg/kg), heavy dose of group (120mg/kg) at random, 10 every group.Gastric infusion is 3 days continuously, fasting is 16 hours after the administration in the 2nd day, and the last administration was drawn dawn 1.2g/kg anesthesia with 20% crow after 90 minutes, the record normal ECG, 3～4 intercostals are opened breast from the left side immediately, expose heart, find out arteria coronaria left anterior descending branch (LAD) in pulmonary conus and left room, wearing one " 0 " number toe-in at distance starting point 2～3mm place pricks, send heart back to thoracic cavity, extrude thoracic cavity inner blood and gas, sew up thoracic wall immediately.Whole surgery was finished in 30 seconds.5,15,30,45,60,90,120,150,180,210, the 240 minutes electrocardiograms in record operation back.
Perform the operation after 360 minutes, the ventral aorta blood sampling, separation of serum is measured serum creatine kinase (CK), lactic acid dehydrogenase (LDH), aspartate aminotransferase (AST) activity according to the described method of detection kit description.Opening breast cores dirty, remove the atrium, the ventricle crosscut is become 3～4, insert 0.25% chlorination nitro blue tetrazolium (NBT) solution of pH 7.4,37 ℃ of dyeing are treated to take out immediately when the infarcted myocardium boundary line is known, separate infarcted myocardium and normal myocardium, weigh calculating myocardium infarction percentage ratio (infarcted myocardium accounts for the percentage ratio of chamber muscle wet weight whole-heartedly) respectively.
Data are represented with x ± SD, and are compared the T-test check with the blank group.
Table 4 soft capsule of the present invention to the influence of rats with myocardial ischemia electrocardiogram J point (x ± SD, n=10)
| Group | Each time point electrocardiogram J point value (mv) after the coronary artery ligation | |||||||
| 5min | 15min | 30min | 60min | 90min | 120min | 180min | 240min | |
| Dosage group soft capsule small dose group of the present invention in the heavy dose of group of the blank group Capsules group of the present invention soft capsule of the present invention soft capsule of the present invention | 0.45±0.18 0.34±0.07 0.31±0.09 * 0.33±0.12 # 0.34±0.14 | 0.44±0.13 0.40±0.13 0.32±0.06 * 0.31±0.1 *# 0.38±0.16 | 0.45±0.1 0.35±0.06 * 0.35±0.08 * 0.30±0.08 **# 0.37±0.14 | 0.39±0.08 0.32±0.04 * 0.30±0.07 * 0.29±0.08 *# 0.34±0.18 | 0.36±0.08 0.3±0.04 * 0.24±0.07 ** 0.30±0.07 # 0.33±0.14 | 0.35±0.06 0.29±0.06 * 0.27±0.09 * 0.30±0.07 # 0.32±0.15 | 0.33±0.06 0.25±0.09 * 0.27±0.09 * 0.26±0.06 *# 0.32±0.14 | 0.31±0.08 0.29±0.07 0.25±0.08 0.28±0.06 # 0.31±0.14 |
Compare with the corresponding time point J of blank group point value
*P＜0.05,
*P＜0.01; Compare with the corresponding time point J of capsule of the present invention point value
#P＞0.05.
Table 5 soft capsule of the present invention to the influence of rats with myocardial ischemia serum CK, LDH, AST activity and myocardial infarction percentage ratio (x ± SD, n=10)
| Group | CK (U·L -1) | LDH (U·L -1) | AST (U·L -1) | Myocardial infarction percentage ratio (%) |
| Dosage group soft capsule small dose group of the present invention in the heavy dose of group of the blank group Capsules group of the present invention soft capsule of the present invention soft capsule of the present invention | 958.4±254.9 703.1±179 * 663.4±269.5 ** 652.5±263.3 *# 773.9±188.2 | 871.4±321.9 471.1±144.1 ** 436.7±177.4 ** 502.3±242.2 *# 746.4±237.0 | 179.8±45 126.8±48.1 * 123.2±19 ** 126.7±24.5 *# 152.9±34.0 | 25.3±3.1 21.2±4.2 * 20.5±3.3 ** 21.0±4.6 *# 24.4±4.9 |
Compare with the blank group
*P＜0.05,
*P＜0.01; Compare with capsule of the present invention
#P＞0.05.
The result is shown in table 4 and table 5, ligation rat coronary artery left anterior descending branch can cause Acute Myocardial Ischemia in Rats, showing as electrocardiogram J point obviously raises, serum creatine kinase, lactic acid dehydrogenase, aspartate aminotransferase activity (content) obviously raise, and myocardial infarction percentage ratio obviously increases.Soft capsule 60mg/kg of the present invention, 120mg/kg and capsule 280mg/kg of the present invention all can suppress raising of electrocardiogram J point in the certain hour scope after coronary artery ligation; Obviously suppress the rising of serum creatine kinase, lactic acid dehydrogenase, aspartate aminotransferase activity (content); Reduce myocardial infarction percentage ratio.The soft capsule of the present invention of same materials medicine and capsule action intensity be (P＞0.05) quite.
Three, the influence that the rat thrombus in vivo is formed
1, gets 50 of rats, be divided into blank group (PEG400) at random, Capsules group of the present invention (280mg/kg), soft capsule small dose group of the present invention (30mg/kg), middle dosage group (60mg/kg), heavy dose of group (120mg/kg), 10 every group.Gastric infusion is 3 days continuously, and fasting is 16 hours after the administration in the 2nd day, and the last administration is after 90 minutes, and (360mg/kg i.p.), separates right carotid and left external jugular vein to chloral hydrate anesthesia, puts into No. seven silk threads that a long 5cm has weighed in polyethylene tube.Be full of polyethylene tube with the normal saline solution that contains heparin sodium (50U/ml), an end of polyethylene tube inserts left external jugular vein, and the other end inserts right common carotid artery.Open folder and close the bulldog clamp of blood vessel, make blood flow flow through polyethylene tube from right general neck artery after, return left external jugular vein.Take out cotton thread immediately behind the open blood flow 15min and weigh, deduct silk thread weight and promptly get wet weight of thrombus.
Data are represented with x ± SD, and are compared the T-test check with the blank group.
Table 6 soft capsule of the present invention to the thrombotic influence of rat artery-vein bypass (x ± s, n=10)
| Group | Wet weight of thrombus (mg) | Suppression ratio (%) |
| Dosage group soft capsule small dose group of the present invention in the heavy dose of group of the blank group Capsules group of the present invention soft capsule of the present invention soft capsule of the present invention | 32.8±9.4 21.2±11.8** 21.3±10.2** 22.3±12.2* # 26.9±12.2 | 35 35 32 18 |
Compare * P＜0.05, * * P＜0.01 with the blank group; Compare with capsule of the present invention
#P＞0.05.
The result is as shown in table 6, there is tangible thrombosis to stick on the silk thread behind the open blood flow 15min, soft capsule 60mg/kg of the present invention, 120mg/kg, capsule 280mg/kg of the present invention all can obviously suppress the formation of thrombosis, with the blank group significant difference (P＜0.05 or P＜0.01) are arranged relatively; The soft capsule of the present invention of same materials medicine and capsule action intensity be (P＞0.05) quite.
Four, to the influence of clotting time of mice
50 of Kunming mouses are divided into blank group (PEG400) at random, Capsules group of the present invention (560mg/kg), soft capsule small dose group of the present invention (60mg/kg), middle dosage group (120mg/kg), heavy dose of group (240mg/kg), 10 every group.Gastric infusion is 3 days continuously, and fasting is 16 hours after the administration in the 2nd day, and the last administration is after 90 minutes, and eye socket is got blood, measures clotting time (experiment is carried out) with slide method under 22 ℃.
Data are represented with x ± SD, and are compared the T-test check with the blank group.
Table 7 soft capsule of the present invention to the influence of clotting time of mice (x ± SD, n=10)
| Group | Clotting time (s) | Rate elongation (%) |
| Dosage group soft capsule small dose group of the present invention in the heavy dose of group of the blank group Capsules group of the present invention soft capsule of the present invention soft capsule of the present invention | 78.3±16.7 98.3±17.9* 106.7±23.4** 98.4±20.5* # 85.0±22.9 | 26 36 26 9 |
Compare * P＜0.05, * * P＜0.01 with the blank group; Compare with capsule of the present invention
#P＞0.05
The result is as shown in table 7, and soft capsule 120mg/kg of the present invention, 240mg/kg, capsule 560mg/kg dosage group clotting time of the present invention obviously are longer than blank group (P＜0.05 or P＜0.01); The soft capsule of the present invention of same materials medicine and capsule action intensity be (P＞0.05) quite.
2, animal is divided into blank group (medical Oleum Glycines) at random, Capsules group of the present invention (280mg/kg), soft capsule group of the present invention (60mg/kg), 90 every group.Continuously gastric infusion is 3 days, and behind the 1st gastric infusion the every 8 hours, respectively give and get 10 rats in batches, chloral hydrate anesthesia (360mg/kg, ip.), separate right carotid and left external jugular vein, in polyethylene tube, put into No. seven silk threads that a long 5cm has weighed.Be full of polyethylene tube with the normal saline solution that contains heparin sodium (50U/ml), an end of polyethylene tube inserts left external jugular vein, and the other end inserts right common carotid artery.Open folder and close the bulldog clamp of blood vessel, make blood flow flow through polyethylene tube from right general neck artery after, return left external jugular vein.Taking out cotton thread immediately behind the open blood flow 15min weighs, deduct silk thread weight and promptly get wet weight of thrombus, and after observing 8h, 16h after the administration, 24h, 32h, 40h, 48h, 56h, 64h, 72h respectively, the weight in wet base of thrombosis, the onset time and the speed of observing capsule of the present invention and soft capsule.
Data are represented with x ± SD, and are compared the T-test check with the blank group.
The table 8 pair thrombotic influence of rat artery-vein bypass (x ± s, n=10)
| Group | 8h | 16h | 24h | 32h | 40h | 48h | 56h | 64h | 72h |
| The blank group | 33.1±10.2 | 32.5±9.6 | 32.7±11.5 | 32.1±9.1 | 34.2±11.9 | 33.4±10.5 | 33.5±9.1 | 32.4±9.9 | 32.8±9.4 |
| Capsules group of the present invention | 32.7±9.8 | 32.1±10.2 | 31.8±9.4 | 31.0±10.4 | 29.6±11.3 | 28.8±9.3 | 26.4±10.8 | 24.6±9.5 | 22.3±12.2* |
| Soft capsule group of the present invention | 32.8±10.5 | 31.5±9.7 | 30.1±9.6 | 29.7±8.8 | 29.2±10.7 | 25.1±8.4 | 24.3±9.7* | 23.9±9.2* | 21.2±11.8* |
Compare with the blank group
*P＜0.05.The result is as shown in table 8, there is tangible thrombosis to stick on the silk thread behind the open blood flow 15min, soft capsule 60mg/kg of the present invention, capsule 280mg/kg of the present invention all can obviously suppress the formation of thrombosis, with the blank group significant difference (P＜0.05 or P＜0.01) are arranged relatively; The soft capsule of the present invention of same materials medicine and capsule action intensity be (P＞0.05) quite.(56h begins onset, with the blank group significant difference is arranged relatively, P＜0.05 but the onset speed of soft capsule of the present invention is faster than capsule of the present invention.)
Above description of test is compared with capsule, and soft capsule has reduced clinical taking dose on the basis that guarantees curative effect.Every 0.4g of capsule, every day 3 times, each 2-4 grain.Every 0.4g of soft capsule, every day 3 times, each 1-2 grain, dosage has reduced half.In addition, onset speed is also faster than capsule.
Drop pill main pharmacodynamics conclusion is identical with soft capsule.
Compared with prior art, the present invention has obviously that dosage is little, technology is refining, and rapid-action, evident in efficacy characteristics have reached the purpose of invention.
For adjuvant and technology that two kinds of dosage form preparations need be selected for use, we have made experimental selection:
For soft capsule:
1, capsule material proportion relation determines
The main component of soft capsule material is that substrate and plasticizer are formed.Its mesostroma material commonly used is a gelatin, plays the effect of soft capsule skeleton; Plasticizer material commonly used is a glycerol, is filled in the gap in the skeleton, can increase the plasticity of rubber.In enduring the glue process, in order to keep the stability of glue, also must add an amount of water, water is unsuitable too many.Water is excessive, and the power of freezing of glue raises, and brings difficulty to glue, also will prolong typing and exsiccant time simultaneously.
Be the influence to the disintegration time of softgel shell of the relation of investigating different proportionings, we are the amount of gelatin and water fixedly, and the glycerol that adds different proportion is investigated:
The different proportionings of table 9 capsule material are to the influence of disintegration time
| Group (n=4) | Proportioning | Disintegration time (minute) | ||
| Gelatin (part) | Glycerol (part) | Water (part) | ||
| 1 2 3 4 | 1 1 1 1 | 0 0.1 0.3 0.6 | 1 1 1 1 | 26 18 13 10 |
By test as can be known, along with the increase of amounts of glycerol, disintegration time shortens gradually.Amounts of glycerol is too much but then, and the soft capsule of preparation is softer, and formability is poor.We are through repetition test, and select gelatin: glycerol: water is 1: 0.3: 1 ratio glue.
2, content prescription research
Content prescription research mainly is the selection of carrying out diluent, and the adjuvant that can be used as diluent in theory in the soft capsule has multiple, as PEG400, and the plant wet goods.We select three kinds of different prescription systems to study and compare, and the proportioning of prescription Chinese medicine composition and each adjuvant sees Table 7.
Three kinds of different prescriptions of table 10
| Prescription 1 | Prescription 2 | Prescription 3 |
| Extract of the present invention (43.0g) Oleum Glycines (57.0g) | Extract of the present invention (43.0g) Cera Flava (2.0g) Oleum Glycines (55.0g) | Extract of the present invention (43.0g) PEG 400 (57.0g) |
Method for making:
Prescription 1 is got the extract of the present invention of recipe quantity, and the Oleum Glycines that adds recipe quantity grinds and evenly gets final product.
Prescription 2 is got the recipe quantity Cera Flava and is melted in the Oleum Glycines of heating, and the extract of the present invention grinding of this solution and recipe quantity is evenly got final product.
Prescription 3 is got the extract of the present invention of recipe quantity, and the PEG-400 that adds recipe quantity grinds and evenly gets final product.
The result: leave standstill the back fast hierarchical by prescription 1 obtained soft capsule content, the part insoluble composition is assembled agglomerating, is difficult to disperse once more, and the water soluble ingredient that contains in the visible medicine and the compatibility of Oleum Glycines are relatively poor, are unfavorable for its homodisperse in Oleum Glycines; After adding Cera Flava in the prescription 2, obviously improved the dispersion effect of extract, but the also corresponding increase of the viscosity of content, the mobile reduction.Simultaneously, leave standstill and still occur after the long period significantly assembling and layering, be unsuitable for making soft capsule; By prescription 3 obtained soft capsule content exquisitenesses, even, after placing, long-time room temperature do not see layering or clustering phenomena yet, and better mobile, be suitable for making soft capsule.
For drop pill:
The substrate that drop pill is commonly used has polyethylene glycol 6000, Macrogol 4000, PEG400, cetomacrogol 1000 0, gelatin, stearic acid, glyceryl monostearate, hydrogenated vegetable wet goods, the present invention select for use fusing point low have the Macrogol 4000 of fine dispersion power and big cohesiveness simultaneously and be used to adjust drop pill hardness, thermostability and mobile PEG6000 carry out the design and the screening of drop pill molding prescription.
The coolant that drop pill is commonly used has liquid paraffin, vegetable oil, methyl-silicone oil etc.Density contrast between coolant and medicinal liquid is the key factor that influences drop pill.In certain density contrast scope, density is approaching more, and the shape of drop pill is round more.And the relative density of drop pill fused mass is more approaching with the relative density (0.970-0.980) of methyl-silicone oil generally all greater than 1, by repeatedly prerun, we select for use the big and cooling effect of proportion preferably methyl-silicone oil be coolant
The prescription design: make substrate with PEG4000 earlier, with even after its fusion with medicament mixed, 80 ℃ of insulations.With 10-15 ℃ methyl-silicone oil is coolant, adds to drip in the drop pill machine to make ball, can be shaped to foundation substantially with drop pill, the minimum proportioning that filters out medicine and substrate is 1: 3, on this basis, replaces PEG4000 with PEG6000, design the substrate prescription of a series of different proportionings, see the following form.
The molding prescription is formed
| The prescription number | Medicine | PEG4000 | PEG6000 |
| 1 2 3 4 | 1 1 1 1 | 3 2 1 0 | 0 1 2 3 |
By medicine and the substrate that table 8 is got each prescription, make drop pill, serve as to investigate index with roundness, dissolve scattered time limit, the hardness of ball.Experimental result shows that when PEG6000 ratio in the mixed-matrix increased, the viscosity of feed liquid was higher, easily hangover, and roundness is poor.And adopt PEG4000 is the drop pill that substrate is made, and its roundness, hardness, dissolve scattered time limit all meet the requirement of drop pill, so the best molding prescription of this experiment sieving drop pill of the present invention is a medicine: PEG4000 is 1: 3.
The specific embodiment
Embodiments of the invention 1: get 15 parts of Rhizoma Chuanxiongs, 15 parts of Radix Angelicae Sinensis, 10 parts of Ramulus Cinnamomi, 8 parts of Olibanums, 8 parts of coarse powder supercritical extractions of Myrrha, get 15 parts of supercritical extractions of Radix Salviae Miltiorrhizae coarse powder, it is standby to merge two stage extracts; 8 parts of Scorpios, 15 parts of Hirudos, 15 parts of coarse powder of Pheretima add ethanol percolation, and it is standby to collect percolate; The medical material of getting behind 10 parts of 15 parts of Radix Paeoniae Rubra, 40 parts of the Radixs Astragali, 8 parts on Flos Carthami, 15 parts in Semen Persicae, 15 parts of Ramulus Moris, 15 parts of Radix Achyranthis Bidentataes, Caulis Spatholobi and supercritical extraction and the percolation merges, water decocts, filtrate decompression concentrates the back precipitate with ethanol, supernatant and percolate are merged, concentrating under reduced pressure, spray drying, it is standby to get dry powder; Get above-mentioned dry powder and supercritical extract, add dispersant, make soft capsule or drop pill.
Embodiments of the invention 2: get 20 parts of Rhizoma Chuanxiongs, 35 parts of Radix Angelicae Sinensis, 15 parts of Ramulus Cinnamomi, 18 parts of Olibanum (processed)s, 10 parts of coarse powder supercritical extractions of Myrrha (processed), get 35 parts of supercritical extractions of Radix Salviae Miltiorrhizae coarse powder, it is standby to merge two stage extracts; 10 parts of Scorpios, 35 parts of Hirudos, Pheretima add ethanol percolation for 20 parts, and it is standby to collect percolate; Get 35 parts of Radix Paeoniae Rubra, 50 parts of the Radixs Astragali, 18 parts on Flos Carthami, 20 parts in Semen Persicae, 35 parts of Ramulus Moris, 20 parts of Radix Achyranthis Bidentataes, 25 parts of Caulis Spatholobis, with the medical material merging behind supercritical extraction and the percolation, water decocts, filtrate decompression concentrates the back precipitate with ethanol, supernatant and percolate are merged concentrating under reduced pressure, spray drying, get dry powder, add supercritical extract, PEG400, colloid mill grinds, glue, the encapsulating machine pelleting, promptly.
Embodiments of the invention 3: get 35 parts of Rhizoma Chuanxiongs, 20 parts of Radix Angelicae Sinensis, 25 parts of Ramulus Cinnamomi, 10 parts of Olibanums, 18 parts of coarse powder supercritical extractions of Myrrha, get 20 parts of coarse powder supercritical extractions of Radix Salviae Miltiorrhizae, it is standby to merge two stage extracts; 18 parts of Scorpios, 10 parts of Hirudos, Pheretima add ethanol percolation for 35 parts, and it is standby to collect percolate; Get 20 parts of Radix Paeoniae Rubra, 80 parts of the Radixs Astragali, 10 parts on Flos Carthami, 35 parts in Semen Persicae, 15 parts of Ramulus Moris, 35 parts of Radix Achyranthis Bidentataes, 15 parts of Caulis Spatholobis, with the medical material merging behind supercritical extraction and the percolation, water decocts, filtrate decompression concentrates the back precipitate with ethanol, and supernatant and percolate are merged concentrating under reduced pressure, spray drying gets dry powder, after sieving, add in the fused Macrogol 4000, stir, add supercritical extract again, stir the back and add in the drop pill machine, drip and make ball, promptly.
Embodiments of the invention 4: 15 parts of the material coarse powder Rhizoma Chuanxiongs of getting it filled, 15 parts of Radix Angelicae Sinensis, 10 parts of Ramulus Cinnamomi, 8 parts of Olibanums, 8 parts of supercritical extractions of Myrrha, extracting pressure 28Mpa, 40 ℃ of extraction temperature extracted 2 hours, and extract is standby; Get 15 parts of supercritical extractions of Radix Salviae Miltiorrhizae coarse powder, extracting pressure 30Mpa, 40 ℃ of extraction temperature, (dehydrated alcohol/medical material, dehydrated alcohol ml/g) extracted 2 hours as entrainer, and extract is standby behind the recovery solvent to use 30% amount.It is standby to merge two stage extracts.Get it filled 20 parts of material coarse powder Scorpios, 15 parts of Hirudos, 15 parts of Pheretimas, (it is standby to collect 10 times of percolates for 70% ethanol/medical material, g/g) percolation to add 70% ethanol.Get it filled 15 parts of material coarse powder Radix Paeoniae Rubra, 40 parts of the Radixs Astragali, 8 parts on Flos Carthami, 15 parts in Semen Persicae, 15 parts of Ramulus Moris, 15 parts of Radix Achyranthis Bidentataes, 10 parts of medical materials of Caulis Spatholobi, merge with the medical material behind supercritical extraction and the percolation, decoct 2 times, the water that at every turn adds 12 times of amounts each 2 hours, merges filtrate, being evaporated to relative density is 1.05 (60 ℃), add 95% ethanol after contain alcohol 65%, with the merging of supernatant and percolate, being evaporated to relative density is 1.1 (60 ℃), spray drying, promptly get dry powder, cross 140 mesh sieves, add supercritical extract, add PEG-400 to 250 part, colloid mill grinds, and in gelatin: glycerol: water is 1: 0.3: 1 ratio glue, the encapsulating machine pelleting.
Embodiments of the invention 5: 27 parts of the thing coarse powder Rhizoma Chuanxiongs of getting it filled, 27 parts of Radix Angelicae Sinensis, 20 parts of Ramulus Cinnamomi, 13 parts of Olibanums (system), 13 parts of supercritical extractions of Myrrha (processed), extracting pressure 28Mpa, 40 ℃ of extraction temperature extracted 2 hours, and extract is standby; Get 27 parts of supercritical extractions of Radix Salviae Miltiorrhizae coarse powder, extracting pressure 30Mpa, 40 ℃ of extraction temperature, (dehydrated alcohol/medical material, dehydrated alcohol ml/g) extracted 2 hours as entrainer, and extract is standby behind the recovery solvent to use 30% amount.Get it filled 13 parts of material coarse powder Scorpios, 27 parts of Hirudos, 27 parts of Pheretimas add 70% ethanol percolation, and (70% ethanol/medical material, ml/g) percolate is standby to collect 10 times of amounts.Get it filled 27 parts of material coarse powder Radix Paeoniae Rubra, 66 parts of the Radixs Astragali, 13 parts on Flos Carthami, 27 parts in Semen Persicae, 27 parts of Ramulus Moris, 27 parts of Radix Achyranthis Bidentataes, 20 parts of Caulis Spatholobis, merge with medicinal residues behind medicinal residues behind the supercritical extraction and the percolation, the water that adds 12 times of amounts decocts each 2 hours 2 times, collecting decoction, being evaporated to relative density is 1.05 (60 ℃), and adding 95% ethanol is 65% to containing the alcohol amount, draws the supernatant, subnatant is centrifugal, centrifugal back supernatant and the supernatant and percolate are merged, and being evaporated to relative density is 1.1 (60 ℃), spray drying, get solid content, after crossing 120 mesh sieves, add in 3 times of fused Macrogol 4000s of amount, stir, add supercritical extract again, stir the back and add in the drop pill machine material-storage jar, keep 80 ℃ of fluid temperature, 60 ℃ of water dropper temperature, regulate and drip speed, drip and make ball.
Claims (6)
1, a kind of Chinese medicine preparation that is used for the treatment of the apoplexy and the thoracic obstruction is characterized in that it is soft capsule or the drop pill of being made by following preparation technology by following materials of weight proportions: 66 parts of the Radixs Astragali, 27 parts of Radix Paeoniae Rubra, 27 parts of Radix Salviae Miltiorrhizaes, 27 parts of Radix Angelicae Sinensis, 27 parts of Rhizoma Chuanxiongs, 27 parts in Semen Persicae, 13 parts on Flos Carthami, 13 parts of Olibanum (processed)s, 13 parts of Myrrha (processed)s, 20 parts of Caulis Spatholobis, 27 parts of Radix Achyranthis Bidentataes, 20 parts of Ramulus Cinnamomi, 27 parts of Ramulus Moris, 27 parts of Pheretimas, 13 parts of Scorpios, 27 parts of Hirudos; The fat-soluble effective ingredient of tanshinone in volatile oil component in supercritical fluid extraction Rhizoma Chuanxiong, Radix Angelicae Sinensis, Ramulus Cinnamomi, Olibanum, the Myrrha and the Radix Salviae Miltiorrhizae, Pheretima, Scorpio, Hirudo take percolation to carry peptide class active substance, then with medicinal residues water boiling and extraction aqueous soluble active constituent behind medicinal residues and the percolation behind Radix Paeoniae Rubra, the Radix Astragali, Flos Carthami, Semen Persicae, Ramulus Mori, Radix Achyranthis Bidentatae, a few flavor medicinal material coarse powder of Caulis Spatholobi and the supercritical extraction, the reuse alcohol deposition method removes destarching, phlegmatic temperament, gummy class water-solubility impurity, adds different adjuvants at last respectively and makes soft capsule or drop pill.
2, the preparation method of the Chinese medicine preparation of the treatment apoplexy according to claim 1 and the thoracic obstruction is characterized in that: get 66 parts of the Radixs Astragali, 27 parts of Radix Paeoniae Rubra, 27 parts of Radix Salviae Miltiorrhizaes, 27 parts of Radix Angelicae Sinensis, 27 parts of Rhizoma Chuanxiongs, 27 parts in Semen Persicae, 13 parts on Flos Carthami, 13 parts of Olibanum (processed)s, 13 parts of Myrrha (processed)s, 20 parts of Caulis Spatholobis, 27 parts of Radix Achyranthis Bidentataes, 20 parts of Ramulus Cinnamomi, 27 parts of Ramulus Moris, 27 parts of Pheretimas, 13 parts of Scorpios, 27 parts of Hirudos; The fat-soluble effective ingredient of tanshinone in volatile oil component in supercritical fluid extraction Rhizoma Chuanxiong, Radix Angelicae Sinensis, Ramulus Cinnamomi, Olibanum, the Myrrha and the Radix Salviae Miltiorrhizae, Pheretima, Scorpio, Hirudo take percolation to carry peptide class active substance, then with medicinal residues water boiling and extraction aqueous soluble active constituent behind medicinal residues and the percolation behind Radix Paeoniae Rubra, the Radix Astragali, Flos Carthami, Semen Persicae, Ramulus Mori, Radix Achyranthis Bidentatae, a few flavor medicinal material coarse powder of Caulis Spatholobi and the supercritical extraction, the reuse alcohol deposition method removes destarching, phlegmatic temperament, gummy class water-solubility impurity, adds different adjuvants at last respectively and makes soft capsule or drop pill.
3, the preparation method of the Chinese medicine preparation of the treatment apoplexy according to claim 2 and the thoracic obstruction is characterized in that: get Rhizoma Chuanxiong, Radix Angelicae Sinensis, Ramulus Cinnamomi, Olibanum, Myrrha coarse powder supercritical extraction, get Radix Salviae Miltiorrhizae coarse powder supercritical extraction, it is standby to merge two stage extracts; Scorpio, Hirudo, Pheretima add ethanol percolation, and it is standby to collect percolate; Get Radix Paeoniae Rubra, the Radix Astragali, Flos Carthami, Semen Persicae, Ramulus Mori, Radix Achyranthis Bidentatae, Caulis Spatholobi, with the medical material merging behind supercritical extraction and the percolation, water decocts, and filtrate decompression concentrates the back precipitate with ethanol, supernatant and percolate are merged, and concentrating under reduced pressure, spray drying, it is standby to get dry powder; Get above-mentioned dry powder and supercritical extract, add Polyethylene Glycol 400, colloid mill grinds, glue, and the encapsulating machine pelleting promptly gets soft capsule.
4, according to the preparation method of the Chinese medicine preparation of claim 2 or the 3 described treatment apoplexy and the thoracic obstruction, it is characterized in that: get Rhizoma Chuanxiong, Radix Angelicae Sinensis, Ramulus Cinnamomi, Olibanum, Myrrha coarse powder supercritical extraction, extracting pressure 28Mpa, 40 ℃ of extraction temperature, extracted 2 hours, extract is standby; Get Radix Salviae Miltiorrhizae coarse powder supercritical extraction, extracting pressure 30Mpa, 40 ℃ of extraction temperature are used dehydrated alcohol/medical material, and the dehydrated alcohol of ml/g 30% amount extracted 2 hours as entrainer, and extract is standby behind the recovery solvent; It is standby to merge two stage extracts; Get Scorpio, Hirudo, Pheretima medical material, powder becomes coarse powder, adds a certain amount of ethanol/medical material, and g/g 70% alcohol dipping was carried out percolation after 24 hours, collects 10 times of percolates, and percolate is standby; Get Radix Paeoniae Rubra, the Radix Astragali, Flos Carthami, Semen Persicae, Ramulus Mori, Radix Achyranthis Bidentatae, Caulis Spatholobi medical material, powder becomes coarse powder, with the medical material merging behind supercritical extraction and the percolation, decoct 2 times, add the water of 12 times of amounts, each 2 hours at every turn, filtered through gauze merges filtrate, and being evaporated to 60 ℃ of relative densities is 1.05, add 95% ethanol to contain alcohol 65% after, left standstill 24 hours, supernatant and percolate are merged, being evaporated to 60 ℃ of relative densities is 1.1, spray drying, it is standby promptly to get dry powder; Got the dry powder and the supercritical extract of 140 mesh sieves, and added PEG400, after stirring, colloid mill grinds, promptly; In gelatin: glycerol: water is 1: 0.3: 1 ratio glue, adopts the encapsulating machine pelleting, promptly gets soft capsule.
5, the preparation method of the Chinese medicine preparation of the treatment apoplexy according to claim 2 and the thoracic obstruction is characterized in that: get Rhizoma Chuanxiong, Radix Angelicae Sinensis, Ramulus Cinnamomi, Olibanum, Myrrha coarse powder supercritical extraction, get Radix Salviae Miltiorrhizae coarse powder supercritical extraction, it is standby to merge two stage extracts; Scorpio, Hirudo, Pheretima add ethanol percolation, and it is standby to collect percolate; Get Radix Paeoniae Rubra, the Radix Astragali, Flos Carthami, Semen Persicae, Ramulus Mori, Radix Achyranthis Bidentatae, Caulis Spatholobi, with the medical material merging behind supercritical extraction and the percolation, water decocts, filtrate decompression concentrates the back precipitate with ethanol, and supernatant and percolate are merged concentrating under reduced pressure, spray drying gets dry powder, after sieving, add in the fused Macrogol 4000, stir, add supercritical extract again, stir the back and add in the drop pill machine, drip and make ball, promptly get drop pill.
6, according to the preparation method of the Chinese medicine preparation of claim 2 or the 5 described treatment apoplexy and the thoracic obstruction, it is characterized in that: get Rhizoma Chuanxiong, Radix Angelicae Sinensis, Ramulus Cinnamomi, Olibanum, Myrrha coarse powder supercritical extraction, extracting pressure 28Mpa, 40 ℃ of extraction temperature, extracted 2 hours, extract is standby; Get Radix Salviae Miltiorrhizae coarse powder supercritical extraction, extracting pressure 30Mpa, 40 ℃ of extraction temperature are used dehydrated alcohol/medical material, and the dehydrated alcohol of ml/g 30% amount extracted 2 hours as entrainer, and extract is standby behind the recovery solvent; Get Scorpio, Hirudo, Pheretima coarse powder and add ethanol/medical material, ml/g 70% alcohol dipping was carried out percolation with the speed of 5ml/min/kg after 24 hours, and it is standby to collect 10 times of amount percolates; Get behind Radix Paeoniae Rubra, the Radix Astragali, Flos Carthami, Semen Persicae, Ramulus Mori, Radix Achyranthis Bidentatae, Caulis Spatholobi medicinal material coarse powder and the supercritical extraction that medicinal residues merge behind the medicinal residues and percolation, soak after 3 hours, the water that adds 12 times of amounts, decoct twice, each 2 hours, collecting decoction, being evaporated to 60 ℃ of relative densities is 1.05, and adding 95% ethanol is 65% to containing the alcohol amount, leaves standstill 24 hours, draw the supernatant, subnatant is centrifugal, and centrifugal back supernatant and the supernatant and percolate are merged, and being evaporated to 60 ℃ of relative densities is 1.1, spray drying promptly gets solid content; After crossing 120 mesh sieves, add in 3 times of fused Macrogol 4000s of amount, stir, make to be uniformly dispersed, add supercritical extract again, stir the back and add in the drop pill machine material-storage jar, keep 80 ℃ of fluid temperature, 60 ℃ of water dropper temperature, regulate and drip speed, drip and make ball, promptly get drop pill.
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| CN1726966B (en) * | 2005-07-27 | 2011-12-14 | 陕西步长制药有限公司 | Preparation of oral disintegration tablet in use for treating disease of apoplexy and obstruction of qi in the chest |
| CN1323683C (en) * | 2005-09-05 | 2007-07-04 | 咸阳步长医药科技发展有限公司 | Medicine composition for treating apoplexy and chest Bi-syndrome and its prepn |
| CN101474269B (en) * | 2008-12-14 | 2011-04-20 | 陕西步长制药有限公司 | Application of pharmaceutical composition in preparing medicament for preventing and treating gynecology disease |
| CN101628054B (en) * | 2009-08-02 | 2011-08-31 | 李述岩 | Medicine for treating ischemic stroke and sequela thereof |
| CN101991616B (en) * | 2009-08-13 | 2012-04-18 | 郝全得 | Traditional Chinese medicine composite for coronary heart disease and angina pectoris and preparation method thereof |
| CN103191178B (en) * | 2012-01-07 | 2018-05-29 | 河北以岭医药研究院有限公司 | A kind of pharmaceutical composition and its preparation of the treatment apoplexy containing frankincense |
| CN102743527B (en) * | 2012-07-04 | 2014-07-16 | 陕西步长高新制药有限公司 | Traditional Chinese medicinal preparation for treating apoplexy and preparation process thereof |
| CN102755474B (en) * | 2012-07-04 | 2014-10-29 | 陕西步长高新制药有限公司 | Chinese medicinal preparation for treating apoplexy and preparation method thereof |
| CN102743529A (en) * | 2012-07-04 | 2012-10-24 | 陕西步长制药有限公司 | Traditional Chinese medicinal preparation for treating apoplexy and preparation process thereof |
| CN102743528A (en) * | 2012-07-04 | 2012-10-24 | 陕西步长制药有限公司 | Traditional Chinese medicinal preparation for treating apoplexy and preparation process thereof |
| CN106975056A (en) * | 2017-04-25 | 2017-07-25 | 李兴尧 | A kind of Chinese medicine microbial fermentation preparation and preparation method and application |
| CN110755485A (en) * | 2019-11-19 | 2020-02-07 | 熊丽 | Medicine for treating pain of upper limbs and preparation method thereof |
| CN114129626A (en) * | 2021-12-20 | 2022-03-04 | 中山大学 | Application of Naoxintong preparation in preparation of medicine for treating non-alcoholic fatty liver disease |
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